Postnatal Changes in Neonatal Acylcarnitine Profile

Abstract

Electrospray-tandem mass spectrometry represents a powerful method for detection of inborn errors of fatty acid metabolism. In the present study, it was used to examine neonatal carnitine metabolism, which reflects fatty acid metabolism. In 70 healthy neonates, blood samples were taken from the umbilical cord and by heel-stick puncture in full-term neonates on postnatal d 5. Cord blood specimens were also obtained from 15 preterm and 10 small-for-gestational-age infants. Acylcarnitine concentrations were measured in dried blood spots by electrospray tandem mass spectrometry. Compared with cord blood, the levels of nearly all acylcarnitine species were significantly higher on the postnatal d 5, whereas free carnitine remained unchanged. Total acylcarnitine/free carnitine-ratio increased, whereas the free carnitine/total carnitine-ratio (0.54 Ϯ 0.05; p Ͻ 0.01) further decreased. A reduced availability of free carnitine in the early neonatal period may affect fatty acid oxidation and thus be of potential pathophysiological relevance under conditions with higher energy demands, e.g. in sepsis. Cord blood concentrations of free carnitine, total carnitine, and total acylcarnitines were strongly related to birth weight (p Ͻ 0.01). Lower umbilical artery pH, i.e. mild hypoxia, caused accumulation of mainly long-chain acylcarnitines. This implicates that long-chain acylcarnitines could serve as a parameter of perinatal asphyxia. In utero, the main substrates for fetal metabolism are amino acids and glucose. The human placenta is also permeable to FFA. However, they are mainly stored as triglycerides in adipose tissues and liver because of the constant supply of glucose and amino acids and a low capacity of fetal tissues for FFA oxidation. The cutoff of the nutrient supply in the presuckling period after birth leads to a transient period of starvation. Thus, the newborn infant is entirely dependent on the mobilization of glycogen and fat stores. With the initiation of milk feeding, neonatal metabolism switches to a high-fat diet. Therefore, it is obvious that fatty acid oxidation is very important in the early postnatal period (1).Carnitine plays an important role in oxidation of especially long-chain fatty acids. Carnitine palmitoyltransferases I and II mediate the transport of fatty acid-carnitine esters (acylcarnitines) across the mitochondrial membranes. Carnitine acyltransferases can also be found in peroxisomes (carnitine octanoyltransferase) and endoplasmatic reticulum (microsomal carnitine acyltransferase), although their function is not yet fully understood. In the mitochondrion, carnitine removes excess acyl groups and thus regulates the concentration of free CoA in the mitochondrial matrix (2). Several studies have shown that the carnitine pool in the neonate is limited (1, 3, 4). Tandem mass spectrometry allows quantitative determination of free carnitine and various carnitine esters like acylcarnitines (5, 6).In the present study, we used this technique to investigate the changes in neonatal carnitine and fat...

Analysis and interpretation of acylcarnitine profiles in dried blood spot and plasma of preterm and full-term newborns

“…A negative correlation with BW and GA was also found in plasma for C 14 Mode of delivery and AC profile. The Kruskal-Wallis test revealed significant differences emerged for some ACs in relation to whether the mode of delivery was vaginal (VD) or cesarean section (CS).…”

“…Box and whisker plots of characteristic short-, medium-, and long-chain acylcarnitines (ACs) in dried blood spots (DBS): (a) free carnitine, (b) C 2 , (c) 2-methylbutyril, (d) C 6 , (e) C 8 , (f) C 10 , (g) C 12 , (h) C 14 , and (i) C 16 . The values are stratified by gestational age (GA) group, from G1 to G4.…”

“…Meyburg compared AC cord blood levels in preterm and full-term infants, correlating them with BW (14), and investigated AC levels longitudinally in DBS of preterm newborn during the first 4 wk of life (15). Another study was recently conducted on amino acids and AC profiles in DBS from preterm newborn (16).…”

Use of Tandem Mass Spectrometry for Multianalyte Screening of Dried Blood Specimens from Newborns

“…Many laboratories acquire FC within the full scan of acylcarnitines (m/z 218 -500), whereas others analyze FC as a separate analyte with its own optimized settings and scan function, such as SRM. Monitoring FC is important for several reasons in addition to disease detection (49,96 ). For example, increased FC in QC samples suggests hydrolysis of acylcarnitines during storage.…”

Preliminary case control study to establish the correlation between novel peroxidation biomarkers in cord serum and the severity of hypoxic ischemic encephalopathy

“…In the experimental setting metabolomic studies performed in animal models of hypoxia reoxygenation have shown that oxidative stress associated metabolites strongly correlate with brain injury. The most specific and reliable biomarkers identified have been isoprostanes, neuroprostanes, non-protein bound iron, and 4-HNE proteins adducts [15][16][17]. F2-isoprostanes have been determined to be both biomarkers and mediators of oxidative stress in numerous diseases [18].…”